Neuroscience
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In the face of inevitable declines in alertness and fatigue resulting from sleep deprivation, effective countermeasures are essential for maintaining performance. External trigeminal nerve stimulation (eTNS) presents a potential avenue for regulating alertness by activating the locus coeruleus and reticular activating system. ⋯ These findings suggested that 120 Hz eTNS stimulation might induce a relaxing effect, and thereby alleviate fatigue while preserving alertness and cognitive performance.
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Down syndrome (DS), caused by trisomy 21, is characterized by intellectual disability and accelerated aging, with chronic oxidative stress contributing to neurological deficits. REST (Repressor Element-1 Silencing Transcription factor), a crucial regulator of neuronal gene expression implicated in DS neuropathology. This study investigates the neuroprotective potential of lithium, a mood stabilizer with known cognitive-enhancing effects, in restoring levels of REST. ⋯ The lithium treatment also significantly reduced ROS levels in the stressed control neurons. These findings reveal a positive association between lithium treatment, REST restoration, and oxidative stress reduction, suggesting that repurposing lithium could contribute to developing therapeutic strategies for DS neuropathologies. This study provides novel insights into DS molecular mechanisms and highlights the potential of lithium as a targeted intervention for improving neuronal function in DS.
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The brain of patients with Parkinson's disease (PD) was characterized by increased phosphorylation and oligomerization of α-synuclein (α-syn) and altered activity of enzymes regulating α-syn phosphorylation and oligomerization. Whether increased α-syn phosphorylation and oligomerization as well as related enzyme changes can be detected in the plasma of PD patients remains unclear. ⋯ Moreover, they were both positively correlated with Hoehn and Yahr staging and polo-like kinase 2 (PLK2, an enzyme promoting α-syn phosphorylation) levels, and negatively correlated with protein phosphatase 2A levels (PP2A, an enzyme dephosphorylating α-syn) and glucocerebrosidase (GCase, an enzyme whose deficiency causes α-syn oligomerization) activity and ceramide (a product of GCase and a natural PP2A activator) levels. The above results suggest that increased α-syn oligomerization and phosphorylation rates and related enzyme changes can be detected in PD plasma and used to discriminate PD patients from HC subjects and predict PD progression.
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Corticosteroid signaling plays a critical role in modulating the neural systems underlying reward and addiction, but the specific contributions of glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs) in the medial prefrontal cortex (mPFC) to opioid reward and dopaminergic plasticity remain unclear. Here, we investigated the effects of intra-mPFC injection of corticosteroid receptor ligand (corticosterone; CORT), glucocorticoid receptor antagonist (RU38486; RU), and mineralocorticoid receptor antagonist (spironolactone; SP) on morphine-induced conditioned place preference (CPP) and dopamine transporter (DAT) expression in the mPFC. Adult male Wistar rats received intra-mPFC injections of CORT, RU, SP, or their respective vehicles prior to morphine CPP conditioning. ⋯ These findings demonstrate that corticosteroid receptor signaling within the mPFC modulates the rewarding properties of morphine and morphine-induced dopaminergic plasticity. This preclinical study suggests that targeting GRs and MRs in the mPFC could be a possible therapeutic approach for treating opioid addiction. By targeting these receptors, it may be possible to reduce opioid reward and counteract the neuroadaptations in dopamine systems associated with addiction.
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Peripuberty is a significant period of neurodevelopment with long-lasting effects on the brain and behavior. Blocking type 1 corticotropin-releasing factor receptors (CRFR1) in neonatal and peripubertal rats attenuates detrimental effects of early-life stress on neural plasticity, behavior, and stress hormone action, long after exposure to the drug has ended. CRFR1 antagonism can also impact neural and behavioral development in the absence of stressful stimuli, suggesting sustained alterations under baseline conditions. ⋯ In the adult amygdala, peripubertal CRFR1a induced alterations in pathways related to neural plasticity and stress in males. In females, pathways related to central nervous system myelination, cell junction organization, and glutamatergic regulation of synaptic transmission were affected. Understanding how acute exposure to neuropharmacological agents can have sustained impacts on brain and behavior, in the absence of further exposures, has important clinical implications for developing adolescents.